JP2008514554A - Hydrogenation of α, β-unsaturated carbonyl compounds. - Google Patents

Abstract

A method for the chemoselective hydrogenation of alpha, beta unsaturated carbonyl compounds is disclosed, in which compounds of the formula R4R3C-CR2-C(O)R1, wherein R1-R4 are as defined herein, are reacted with a hybrid donor to form a compound of formula R4R3CH-CH(R2)-C(O)R1, in which R1-R4 are as above. That method permits the selective hydrogenation of alpha, beta unsaturated aldehydes and ketones without the use of metal catalysts.

Description

  The present invention relates to a process for the hydrogenation of α, β-unsaturated carbonyl compounds.

  Branched carbonyl compounds become a wide variety of intermediates in the synthesis of pharmaceuticals, odorants, natural products, and other functional substances. For example, citronellal is a β-branched aldehyde that is used as an odorant and also as an important material for industrial synthesis of citronellol, menthol, muscone and α-tocopherol. Interestingly, citronellates obtained from nature are not enantiomerically pure. Therefore, a process that can be synthesized enantiomerically pure is important. Scheme 1:

  Shows an example of industrial use of β-branched aldehyde.

  Methods for enantiomerically purifying branched carbonyl compounds include catalytic asymmetric hydrogenation and conjugated reduction of α, β-unsaturated carbonyl compounds corresponding to them. Scheme 2:

  Shows hydrogenation of an α, β-unsaturated carbonyl compound.

  The above two chemical reaction examples are described in the literature and are based on metal catalysis, and catalytic asymmetric hydrogenation has been successfully used only with ketones, but not with aldehydes. Furthermore, there is a problem that existing processes are often not chemoselective. In many cases, the functional group is also reduced in the same way as the double bond in this case. This is not a preferred reaction. Also, enantioselectivity is often insufficient. Catalytic asymmetric hydrogenation of aldehydes has not been fully achieved.

  Furthermore, the metal catalyzed reaction also has the problem that the hydrogenating agent used requires a hydrogen gas pressure higher than atmospheric pressure. Usually, the use of gaseous reactants makes the device very complex. Furthermore, there is a problem that an excellent metal catalyst is very expensive. Thus, the catalyst must not only be able to be removed from the final product, but must be provided with additional steps to allow the use of the expensive metal fraction.

  The present invention aims to provide a single process for preparing branched carbonyl compounds. This invention does not require the use of a metal catalyst, and is a process that can be used for aldehydes without being limited to ketones.

  The present invention provides a method for hydrogenation of an α, β-unsaturated carbonyl compound, which has the general formula (I):

(Where
R ¹ is H, a branched or unbranched chain that contains 1 to 30 carbon atoms and may contain an appropriate substituent, and may contain one or more heteroatoms in the carbon chain, and is saturated. Or an unsaturated hydrocarbon radical, or an aryl or heteroaryl group that may contain suitable substituents,
R ² , R ³ and R ⁴ are the same or different and are each H, F, Cl, Br, I, OH, CN, NO ₂ , NO, SO ₂ , SO ₃ ⁻ , amino, mono- or di- (C ₁ -C ₂₄ - alkyl) - substituted amino, mono- - or di - (C ₅ -C ₂₀ - aryl) - substituted amino, imino, phosphono, phosphonato (phosphonato), phosphinato (phosphinato), phospho, phosphino, 1-30 Branched or unbranched, saturated or unsaturated hydrocarbon radicals containing one carbon atom and may contain suitable substituents and may contain one or more heteroatoms in the carbon chain, or Represents an aryl or heteroaryl group which may contain suitable substituents;
In each case, two or more of the R ¹ , R ² , R ³ , and R ⁴ radicals are aromatic compounds, alicyclic compounds, heterocyclic aromatic compounds, and alicyclic compounds that are heterocyclic rings. Or a fused 5-membered ring and / or a 6-membered ring, and may have up to 4 substituents. )

A compound of the formula (II) reacts with a hydride donor:

It becomes the compound of this.
(Where
R ¹ , R ² , R ³ and R ⁴ are as defined above)

  The present invention allows α, β-unsaturated carbonyl compounds to be reduced by catalysis in a highly chemoselective manner, eliminating the use of metal catalysts. Two methods have been developed according to the invention, first suitable for nonasymmetric reduction to form a racemic mixture and second suitable for advanced enantioselective reduction. .

  Scheme 3 showing an example reaction of an α, β-unsaturated carbonyl compound using dihydropyridine as a hydride donor:

  Is used to describe an embodiment of the method according to the invention. Scheme 3 represents the hydrogenation of an α, β-unsaturated carbonyl compound with a metal-free catalyst, where an amine or ammonium salt is used.

R ¹ , R ² , R ³ and R ⁴ are each defined above. Branched or unbranched, saturated or unsaturated hydrocarbon radicals having 1 to 30 carbon atoms are C ₁ -C ₂₄ -alkyl, C ₂ -C ₂₄ -alkenyl, C ₂ -C ₂₄ - alkynyl, C ₁ -C ₂₄ - alkoxy, C ₂ -C ₂₄ - alkenyloxy, C ₂ -C ₂₄ - alkynyloxy, C ₅ -C ₃₀ - aryl, C ₅ -C ₃₀ - aryloxy, C ₂ -C ₂₄ -alkoxyalkyl, C ₆ -C ₃₀ -aryloxyalkyl, hydroxyl, sulfhydryl, C ₂ -C ₂₄ -alkylcarbonyl, C ₆ -C ₃₀ -arylcarbonyl ), C ₂ -C ₂₄ - alkoxycarbonyl _{(alkoxycarbonyl), C 6 -C 30} - aryloxycarbonyl (aryloxy-carbonyl), halocarbonyl _{(halocarbonyl), C 2 -C 24} - alkylcarbonyl isocyanatomethyl (alkylcarbonato), C ₆ -C ₃₀ - aryl-carbonitrile Preparative (Arylcarbonato), carboxyl, carboxylato (Carboxylato), carbamoyl (Carbamoyl), mono - and di - (C ₁ -C ₂₄ - alkyl) - substituted carbamoyl _{(mono- and di- (C 1 -C} 24 -alkyl) -substituted carbamoyl), C ₂ -C ₂₄ -alkylamido, C ₆ -C ₃₀ -arylamido, C ₂ -C ₂₄ -alkylimino, C ₆ -C ₃₀ -arylimino ( arylimino), C ₁ -C ₂₄ -alkylsulfanyl, C ₅ -C ₃₀ -arylsulfanyl, C ₁ -C ₂₄ -alkylsulfinyl, C ₅ -C ₃₀ -arylsulfinyl C ₁ -C ₂₄ -alkylsulfonyl and C ₅ -C ₃₀ -arylsulfonyl are preferably selected.

  “Alkyl” means a straight, branched or cyclic hydrocarbon radical having predominantly 1 to 30 carbon atoms, preferably 1 to 24 carbon atoms, such as methyl, ethyl, This includes not only n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, octyl, decyl, but also cycloalkyl groups such as cyclopentyl, cyclohexyl and the like. The hydrocarbon radical has preferably 1 to 18 carbon atoms, particularly preferably 1 to 12 carbon atoms.

  “Alkenyl” means a straight, branched or cyclic hydrocarbon radical having at least one double bond and predominantly 2 to 30 carbon atoms, preferably 2 to 24 carbon atoms, For example, ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl , Hexadecenyl, eicosenyl, tetracosenyl and the like, as well as cycloalkenyl groups such as cyclopentenyl and cyclohexenyl. The alkenyl radical has preferably 2 to 18 carbon atoms, particularly preferably 2 to 12 carbon atoms.

  “Alkynyl” means a straight, branched or cyclic hydrocarbon radical having at least one triple bond and predominantly 2 to 30 carbon atoms, preferably 2 to 24 carbon atoms, for example Ethynyl, n-propynyl, isopropynyl, n-butynyl, isobutynyl, octynyl, decynyl, tetradecynyl, Examples include hexadecynyl, eicosynyl, and tetracosynyl. The number of carbon atoms possessed by the alkynyl radical is preferably 2 to 18, particularly preferably 2 to 12 carbon atoms.

  Preferred alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butyloxy, isobutyloxy, t-butyloxy ( t-butyloxy), pentyloxy, hexyloxy and the like.

The aryl group used in the present invention is an aromatic ring system having 5 to 30 carbon atoms, and this aromatic ring optionally contains heteroatoms such as N, O, S, P and Si. May be. Said aromatic rings are single ring systems or multiple ring systems which are, for example, fused rings or rings linked together via single or multiple bonds. Examples of the aromatic ring include phenyl, naphthyl, biphenyl, diphenyl ether, diphenylamine, benzophenone, and the like. The substituted aryl group includes one or more substituents specified in the definition of R ¹ above. Examples of heteroalkyl groups include alkoxyalkyl-alkylsulfanyl-substituted alkyl, N-alkylated aminoalkyl, and the like. Examples of heteroaryl substituents include pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl, imidazolyl 1,2,4-triazolyl (1,2,4-triazolyl), tetrazolyl and the like. Examples of alicyclic atomic groups containing heteroatoms include pyrrolidino, morpholino, piperazino, and piperidino.

Examples of the substituent of the above atomic group include OH, F, Cl, Br, I, CN, NO ₂ , NO, SO ₂ , SO ₃ ⁻ , amino, mono- or di- (C ₁ -C ₂₄ -alkyl). There are -substituted amino, mono- or di- (C ₅ -C ₂₀ -aryl) -substituted amino or imino, which may be substituted in turn. In particular, cyclic radicals may also contain C ₁ -C ₆ -alkyl groups as substituents.

As functional groups, the radicals or substituents defined above may contain any atomic group known in the prior art and commonly used in the field of organic synthesis. For example, halogen, hydroxyl group, sulfhydryl group, C ₁ -C ₂₄ -alkoxy, C ₂ -C ₂₄ -alkenyloxy, C ₂ -C ₂₄ -alkynyloxy, C ₅ -C ₂₀ -aryloxy, C ₂ Acyl such as -C ₂₄ -alkylcarbonyl (-CO-alkyl) and C ₆ -C ₂₀ -arylcarbonyl (-CO-aryl), acyloxy (-O-acyl), C ₂ -C ₂₄ -Alkoxycarbonyl (-(CO) -O-alkyl), C ₆ -C ₂₀ -aryloxycarbonyl (-(CO) -O-aryl), halocarbonyl (-(CO ) -X, wherein X is halogen), C ₂ -C ₂₄ -alkylcarbonato (-O- (CO) -O-alkyl), C ₆ -C ₂₀ -arylcarbonato (- O-(CO) -O- aryl), carboxyl (-COOH), carboxylato (-COO ^-), carbamoyl _{(- (CO) -NH 2)} , Substituted C ₁ -C ₂₄ - alkylcarbamoyl (- (CO) -NH (C 1 -C 24 - alkyl)), di-substituted C ₁ -C ₂₄ - alkylcarbamoyl (- (CO) -N (C 1 -C 24 -Alkyl) ₂ ), monosubstituted arylcarbamoyl (-(CO) -NH-aryl), thiocarbamoyl (-(CS) -NH ₂ ), carbamido (-NH- (CO) -NH _2), cyano (-C≡N), isocyano ^{(isocyano) (- N + ≡C} -), cyanato (cyanato) (- OC≡N), isocyanato ^{(isocyanato) (- ON + ≡C} -), isothiocyanato ( isothiocyanato) (- SC≡N), azido ^{(-N = N + = N -} ), formyl (formyl) (- (CO) -H), thioformyl (thioformyl) (- (CS) -H), amino (- NH _2), mono - and di - (C ₁ -C ₂₄ - alkyl) - substituted amino _{(mono- and di- (C 1 -C} 24 -alkyl) -substituted amino), mono - and di - (C ₅ - C ₂₀ - aryl) - substituted amino _{(mono- and di- (C 5 -C} 20 -aryl) -substituted amino), C 2 -C 24 - alkyl amide (-NH- (CO) - Alkyl), C ₅ -C ₂₀ - aryl amide (-NH- (CO) - aryl), imino (-CR = NH, wherein R is, H, C ₁ -C ₂₄ - alkyl, C ₅ -C ₂₀ - Aryl, C ₆ -C ₂₀ -alkaryl, C ₆ -C ₂₀ -alkyl, etc.), alkylimino (-CR = N (alkyl), where R is H, alkyl, aryl, alkaryl ), Arylimino (-CR = N (aryl), where R is H, alkyl, aryl, alkaryl, etc.), nitro (-NO ₂ ), nitroso (-NO), sulfo (-SO ₂ -OH) , sulfonato _{(sulfonato) (- SO 2 -O} -), C 1 -C 24 - alkylsulfanyl (alkylsulfanyl) (- S- alkyl: also referred to as "alkylthio (alkylthio)"), ant - Rusurufaniru (arylsulfanyl) (- S-aryl: also called “arylthio”), C ₁ -C ₂₄ -alkylsulfinyl (— (SO) -alkyl), C ₅ -C ₂₀ -arylsulfinyl (ary lsulfinyl) (-(SO) -aryl), C ₁ -C ₂₄ -alkylsulfonyl (-SO ₂ -alkyl), C ₅ -C ₂₀ -arylsulfonyl (-SO ₂ -aryl), phosphono (-P (O) (OH) _2), phosphonate ^{(-P (O) (O -} ) 2), phosphinato ^{(-P (O) (O -} )), phospho (-PO _2), phosphino (-PH ₂₎ include, In the case of alkyl, the hydrocarbon radical is C ₁ -C ₂₄ -alkyl, preferably C ₁ -C ₁₈ -alkyl, more preferably C ₁ -C ₁₂ -alkyl, particularly preferably C _1- C ₆ -alkyl. In the case of alkenyl, it is C ₂ -C ₂₄ -alkenyl, preferably C ₂ -C ₁₈ -alkenyl, more preferably C ₂ -C ₁₂ -alkenyl, particularly preferably C ₂ -C ₆ -alkenyl. . In the case of alkynyl, it is C ₂ -C ₂₄ -alkynyl, preferably C ₂ -C ₁₈ -alkynyl, more preferably C ₂ -C ₁₂ -alkynyl, particularly preferably C ₂ -C ₆ -alkynyl. . In the case of aryl, it is C ₅ -C ₃₀ -aryl, preferably C ₅ -C ₂₀ -aryl, more preferably C ₅ -C ₁₂ -aryl. In the case of aralkyl, it is C ₆ -C ₃₀ -aralkyl, preferably C ₆ -C ₂₀ -aralkyl, more preferably C ₆ -C ₁₂ -aralkyl.

  In the present invention, the compound of general formula (I) reacts with a hydride donor. Any compound that releases hydrogen ions can be used as a hydride donor, but organic hydride donors are preferred. Suitable hydride donors include, for example, Hanzsch dihydropyridine. As an embodiment of the present invention, the general formula (III):

It is preferred to use dihydropyridines of the general formula (III).
(Where
R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are the same or different and each is H, OH, saturated or unsaturated, linear, branched or cyclic, unsubstituted or substituted C ₁ -C ₂₀ -alkyl radical, halogen (especially F, Cl, Br, I), NO ₂ , amino group, —CO ₂ R ¹⁰ , C (O) R ¹¹ , COR ¹² , OR ¹³ (where R ¹⁰ ~ R ¹³ is each H, a branched or unbranched chain having 1 to 30 carbon atoms, may contain suitable substituents, and may have one or more heteroatoms in the chain. A saturated or unsaturated hydrocarbon radical), or an aryl or heteroaryl group which may have an appropriate substituent. R ¹⁹ is H, a branched or unbranched chain which may have 1 to 30 carbon atoms and may contain suitable substituents and may have one or more heteroatoms in the chain and is saturated. Alternatively, it is an unsaturated hydrocarbon radical, or an aryl group or heteroaryl group which may have an appropriate substituent. )

Among the compounds of the general formula (III), R ⁵ and R ⁸ are halogen, NO ₂ , —CO ₂ R ¹⁰ , C (O) R ¹¹ , COR ¹² , OR ¹³ (R ^{10 to} R ¹³ are each of the above Are preferably selected from electron-withdrawing radicals such as those defined in. R ⁶ and R ⁷ are preferably H or a C ₁ -C ₆ -alkyl group. R ⁹ is preferably H or a C ₁ -C ₆ -alkyl group, and R ¹⁹ is preferably H or a C ₁ -C ₆ -alkyl group.

  Further examples of hydride donors include secondary alcohols, silanes, triarylmethanes, cyclohexadienes, formaldehyde and derivatives thereof, formic acid and derivatives thereof, and salts of these compounds.

  The selectivity and efficiency of the process according to the invention are further improved when reacted with a catalyst. If a catalyst is used for this reaction, the configuration may be affected. In one embodiment, the catalyst is preferably an organic base (especially a primary amine, a secondary amine or an acid addition salt of the amine), in particular the general formula (IV):

Or amine acid addition salts thereof are preferred.
(Where
R ¹⁴ is H, a saturated or unsaturated, branched or straight chain alkyl group, alkenyl group, alkynyl group, aryl or alkylaryl, which may contain a suitable substituent, or a suitable substituent. Represents a hydrocarbon group containing a heteroatom which may contain a group,
R ¹⁵ is a saturated or unsaturated, branched or straight chain alkyl group, alkenyl group, alkynyl group, aryl or alkylaryl, which may contain a hydrocarbon group which may contain a suitable substituent, or a suitable substituent. Represents a hydrocarbon group containing a heteroatom that may contain,
R ¹⁴ and R ¹⁵ may form a condensed ring having 3 to 7 carbon atoms, or a substituted or unsubstituted ring, and in addition to the nitrogen atom of the general formula (IV), another hetero atom May also be included. )

When both R ¹⁴ and R ¹⁵ are ring systems, the radical is preferably selected to be a 5-membered or 6-membered alicyclic or aromatic compound, such as pyrrolidinyl, piperidinyl, morpholinyl. (Morpholinyl), pyrrolyl, pyridinyl, pyrimidinyl, imidazolyl and the like.

Suitable salts for forming the acid addition salts are selected from inorganic acids and organic acids. In the case of inorganic acids, especially selected from HCl, H ₂ SO ₄ , H ₂ SO ₃ , HNO ₃ , HNO ₂ , HClO ₄ , H ₃ PO ₄ , chromic acid and suitable combinations of these inorganic acids. In the case of organic acids, it is particularly preferred to select from carboxylic acids, sulfonic acids, phosphonic acids and phenols having 1 to 5 electron withdrawing substituents. Examples of suitable organic acids are acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 2-nitrobenzoic acid , Cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, trifluorosulfonomethane acid, p-toluenesulfonic acid, salicylic acid, chloroacetic acid, dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid, these organic acids And the like.

The compounds of the general formula (IV) used are preferably secondary amines, ie R ¹⁴ is not hydrogen. For non-asymmetric treatment, it is preferred to use non-chiral amines, for example R ¹⁴ and R ¹⁵ are methyl, ethyl, propyl, butyl, cyclopentyl, cyclohexyl, respectively. , A compound selected from the group consisting of cyclooctyl, phenyl, naphthyl, benzyl and trimethylsilyl. Preferred is an amine in which a nitrogen atom and the above R ¹⁴ or R ¹⁵ radical form a ring of 3 to 15 atoms (the amine may optionally contain a substituent), particularly at least one chiral center in the molecule. It is preferred to use amines having Particularly preferred compounds are those of the general formula (V):

It was found to be imidazolidinone and its derivatives as shown in FIG.
(Where
R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are the same or different and are each H, OH, F, Cl, Br, I, NO ₂ , NO, SO ₂ , SO ₃ ⁻ , amino, mono- or di- (C ₁ -C ₂₄ -alkyl) -substituted amino, mono- or di- (C ₅ -C ₂₀ -aryl) -substituted amino, imino, phosphono, phosphonato, phosphinato, phospho, phosphino, 1-30 carbon atoms A branched or unbranched, saturated or unsaturated hydrocarbon radical which may have one or more heteroatoms in the chain, or a suitable substituent Represents an aryl group or heteroaryl group which may contain
R ¹⁷ and / or R ¹⁸ radicals, including R ²⁰ , may form a 5-membered or 6-membered ring that is an aromatic, alicyclic, heteroaromatic or heteroalicyclic compound. Furthermore, you may have 4 or less substituents.
R ²⁰ is hydrogen, a saturated or unsaturated, branched or straight chain alkyl group, alkenyl group, alkynyl group, aryl or alkylaryl, which may contain a suitable substituent, or a suitable substituent. The hydrocarbon group containing the hetero atom which may contain a group is represented. )

  The catalyst is preferably used in an amount of 0.1 to 100 mol%, more preferably 1 to 30 mol%, particularly 0.1 to 10 mol%, relative to the amount of the compound of the general formula (I). preferable.

As a further exemplary embodiment of the invention, in addition to the catalyst of general formula (IV), dihydropyridines of general formula (III) identified as hydride donors may also be used as cocatalysts. In this example embodiment, when H ₂ is fed to the reaction mixture, the pyridine formed by oxidation by forming a hydride is immediately reduced back to dihydropyridine. Thus, pyridine can be reused for the hydrogenation of the carbonyl compound. This method has the advantage that only a small amount of the reaction part of the hydride donor is required and a relatively inexpensive hydrogen gas only needs to be continuously supplied. For example, pyridine is reduced by H ₂ by appropriate chemical catalysis or enzyme catalysis. Instead of H _2, it is also possible to use other reducing agents or electrochemical methods.

  In carrying out the process according to the invention, the starting materials used (ie compounds of general formula (I)), the hydride donor and the catalyst are dissolved or suspended in a suitable solvent which does not adversely influence the reaction. When any of the reaction components (for example, hydride donor) is present as a gas, the solid component or liquid component is dissolved or suspended in the solvent, and the gas component is continuously introduced into the solution. .

  The reaction is preferably carried out at standard pressure. If one reactant (eg a hydride donor) is present in the gaseous state, the reactant may be reacted under a pressure of, for example, 0.1 to 200 bar, preferably 0. A pressure of 5 to 50 bar, more preferably a pressure of 0.5 to 5 bar.

  In the above reaction, the reaction temperature is not a problem. The said reaction can be performed between -100 degreeC-100 degreeC, and -90 degreeC-50 degreeC is preferable. In order to avoid the formation of by-products as much as possible, the above reaction is preferably performed in an inert gas atmosphere.

  After completion of the reaction, the reaction product can be separated by a known technique. Usually, the solvent is removed and the resulting crude product is a well-known method in the art (eg chromatography, distillation, sublimation, crystallization, recrystallization, extraction, etc.) To be purified.

Example 1. The non-asymemtric conjugated reduction of Hanzsch ester 1 by α, β-unsaturated aldehydes 3a and 3I was catalyzed by the dibenzylammonium salt of trifluoroacetic acid ( Scheme 4 showing the synthesis of o-nitrophenyl) propanalaldehyde (4a):

Will be described.
Example 1
To a solution of o-nitrocinnamaldehyde 3a (88.6 mg, 0.5 mmol) and catalyst 2a (7.8 mg, 0.025 mmol, 5 mol%) in anhydrous THF (2 ml) was added dihydropyridine 1 (140 mg, 0.8 mmol). 55 mmol, 1.1 chemical equivalents) was added. The reaction mixture was stirred at room temperature for 5 hours under an argon gas atmosphere. The solvent was then removed and the residue was chromatographed on silica gel (30% diethyl ether / n-hexane). As oil, 84 mg (94%) of 3- (o-nitrophenyl) -propanal (4a) was obtained.

  In the same manner as in Example 1, the compounds shown in the following table were obtained by the reaction.

2. Asymmetric conjugate reduction of α, β-unsaturated aldehyde using catalyst 5.
Example 2
Synthesis of (R) -4- (1-methyl-3-oxopropyl) benzonitrile ((R) -4- (1-methyl-3-oxopropyl) benzonitrile).
(E)-or (Z) -4- (1-methyl-3-oxopropenyl) benzonitrile (0.5 mmol) (or E / Z mixture) and catalyst 5 (10 mol%) in anhydrous dioxane (7 ml) Was added dihydropyridine 6 (1.1 chemical equivalents). The reaction mixture was stirred at 13 ° C. for 36 hours under an argon gas atmosphere. The solvent was then removed and the residue was subjected to silica gel chromatography. (R) -4- (1-Methyl-3-oxopropyl) benzonitrile was obtained in a yield of 90%, and the enantiomeric ratio was 97.5: 2.5. Scheme 5 which is the above embodiment of the present invention:

  Other various unsaturated aldehydes could also be reacted in the same manner as described above.

Example 3
For the hydrogenation of ketones, Scheme 6:

  Shown in Dihydropyridine 1 (1.1 chemical equivalent) was added to a solution of 3-methylcyclohexenone (0.5 mmol) and catalyst (0.1 mmol, 20 mol%) in anhydrous 1,4-dioxane (2 ml). The reaction mixture was stirred at room temperature for 4 days under an argon gas atmosphere. The solvent was then removed and the residue was chromatographed on silica gel (30% diethyl ether / n-hexane). The ketone was separated with an enantiomeric excess of 59% (ee value).

Claims (8)

Formula (I):
(Where
R ¹ is H, a branched or unbranched chain that contains 1 to 30 carbon atoms and may contain an appropriate substituent, and may contain one or more heteroatoms in the carbon chain, and is saturated. Or an unsaturated hydrocarbon radical, or an aryl or heteroaryl group that may contain suitable substituents,
R ² , R ³ , R ⁴ are the same or different and are each H, F, Cl, Br, I, OH, CN, NO ₂ , NO, SO ₂ , SO ₃ ⁻ , amino, mono- or di- ( (C ₁ -C ₂₄ -alkyl) -substituted amino, mono- or di- (C ₅ -C ₂₀ -aryl) -substituted amino, imino, phosphono, phosphonato, phosphinato, phospho, phosphino, 1-30 carbon atoms A branched or unbranched, saturated or unsaturated hydrocarbon radical that may contain one or more heteroatoms in the carbon chain, or a suitable substituent. Represents an aryl group or a heteroaryl group which may be included,
In each case, two or more of the R ¹ , R ² , R ³ , and R ⁴ radicals are aromatic compounds, alicyclic compounds, heterocyclic aromatic compounds, and alicyclic compounds that are heterocyclic rings. A 5-membered ring or a 6-membered ring or a condensed 5-membered ring and / or a 6-membered ring, and may have a maximum of 4 substituents)
Is reacted with a hydride donor to give a compound of the general formula (II):
(Where
R ¹ , R ² , R ³ and R ⁴ are as defined above)
A method for hydrogenating an α, β-unsaturated carbonyl compound, which is a compound represented by the formula:   The hydride donor is at least one compound selected from the group consisting of dihydropyridines, secondary alcohols, silanes, triarylmethanes, cyclohexadiene, formaldehyde and derivatives thereof, formic acid and derivatives thereof, and salts of the compounds. The method of claim 1, wherein: Said hydride donor is represented by the general formula (III):
(Where
R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are the same or different and are each independently H, OH, saturated or unsaturated, linear, branched or cyclic, unsubstituted or substituted C _1- C ₂₀ -alkyl radical, halogen, NO ₂ , amino group, —CO ₂ R ¹⁰ , C (O) R ¹¹ , COR ¹² , OR ¹³ (wherein R ^{10 to} R ¹³ are H, 1 to A branched or unbranched, saturated or unsaturated hydrocarbon radical which has 30 carbon atoms and may contain suitable substituents and may have one or more heteroatoms in the chain) Or an aryl group or heteroaryl group which may have an appropriate substituent,
R ¹⁹ is H, a branched or unbranched chain which may have 1 to 30 carbon atoms and may contain suitable substituents and may have one or more heteroatoms in the chain and is saturated. Or an unsaturated hydrocarbon radical, or an aryl or heteroaryl group which may have an appropriate substituent)
The method according to claim 2, wherein the salt is a dihydropyridine represented by the formula (II) or a salt of the compound represented by the general formula (III).   The method according to any one of claims 1 to 3, wherein the hydrogenation method is carried out in the presence of a catalyst.   The method according to claim 4, wherein the catalyst is an organic base.   The method according to claim 5, wherein the organic base is an amine or an acid addition salt of an amine. The catalyst is represented by the general formula (IV):
(Where
R ¹⁴ is H, a saturated or unsaturated, branched or straight chain alkyl group, alkenyl group, alkynyl group, aryl or alkylaryl, which may contain a suitable substituent, or a suitable substituent. Represents a hydrocarbon group containing a heteroatom which may contain a group,
R ¹⁵ is a saturated or unsaturated, branched or straight chain alkyl group, alkenyl group, alkynyl group, aryl or alkylaryl, which may contain a hydrocarbon group which may contain a suitable substituent, or a suitable substituent. Represents a hydrocarbon group containing a heteroatom that may contain,
R ¹⁴ and R ¹⁵ may form a condensed ring having 3 to 7 carbon atoms, or a substituted or unsubstituted ring, and in addition to the nitrogen atom of the general formula (IV), another hetero atom May also be included)
The method according to claim 5, wherein the amine is represented by the formula: The amine is represented by the general formula (V):
(Where
R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are the same or different and are each H, OH, F, Cl, Br, I, NO ₂ , NO, SO ₂ , SO ₃ ⁻ , amino, mono- or di- (C ₁ -C ₂₄ -alkyl) -substituted amino, mono- or di- (C ₅ -C ₂₀ -aryl) -substituted amino, imino, phosphono, phosphonato, phosphinato, phospho, phosphino, 1-30 carbon atoms A branched or unbranched, saturated or unsaturated hydrocarbon radical which may have one or more heteroatoms in the chain, or a suitable substituent Represents an aryl group or heteroaryl group which may contain
R ¹⁷ and / or R ¹⁸ radicals, including R ²⁰ , may form a 5-membered or 6-membered ring that is an aromatic, alicyclic, heteroaromatic or heteroalicyclic compound. And may further have 4 or less substituents,
R ²⁰ is H, a saturated or unsaturated, branched or straight chain alkyl group, alkenyl group, alkynyl group, aryl or alkylaryl, which may contain a suitable substituent, or a suitable substituent. Represents a hydrocarbon group containing a hetero atom which may contain a group)
The method according to claim 7, which is represented by the formula: